Calcium metabolism

Thomas Mathew
1st year pg
Orthopaedics department
Pushpagiri medical college
 CONTENTS
• DISTRIBUTION
• BODY REQUIREMENTS
• BIOLOGICAL FUNCTIONS OF CALCIUM
• CALCIUM HOMEOSTASIS-ABSORPTION
• FACTORS CONTROLLING ABSORPTION
• HORMONAL CONTROL OF CALCIUM & PHOSPHATE METABOLISM
VITAMIN D
PTH
CALCITONIN
OTHER HORMONES
• EXCRETION OF CALCIUM AND PHOSPHOROUS
• HYPOCALCEMIA AND HYPERCALCEMIA
 Different Forms of Calcium
• Most of the calcium in the body exists as the mineral
hydroxyapatite, Ca10(PO4 )6 (OH)2 .

Calcium in the plasma:

• 45% in ionized form (the physiologically active form)
• 45% bound to proteins (predominantly albumin)
• 10% complexed with anions (citrate, sulfate, phosphate)

• Both total calcium and ionized calcium measurements are

available
DISTRIBUTION
 Body requirements
Age (in years) Calcium Requirement

1–3 500mg
4-8 800mg
9 - 18 1300mg
19 - 50 1000mg
51+ 1500mg

*Pregnant and lactating women are recommended a daily

calcium intake of 1000mg
Biological functions of Calcium
 SOURCE

Natural sources
• Milk and milk products – 1L of cows milk contain 1200mg of Ca
• Green leafy vegetables
• Fish
• Fruits – custard apple , dried fruits , apricots
• Cereals – ragi
• Egg yolk
• Beetel leaves with lime
Calcium preparations
• Calcium chloride -27% ca – usually not
preferred
• Calcium gluconate – 9% ca preferred
• Calcium lactate -13% ca given orally
• Calcium dibasic phosphate – 23%
• Calcium carbonate -40% ca
 Calcium Homeostasis
• Two systems involved

• Major organ system i.e intestine,kidney and

bone

• Major hormone involved are parathyroid

hormone ,active vitamin D3 and calcitonin
 ABSORPTION OF CALCIUM

 Calcium is taken through dietary sources as calcium phosphate, carbonate,

tartrate and oxalate.
 It is absorbed from the gastrointestinal tract in to
• blood and distributed to various parts of the body.

Two mechanisms have been proposed for the absorption of

calcium by gut mucosa:

 Simple Diffusion.
 An active transport process, involving energy
and calcium pump.
 Passive Absorption Of Calcium
• Paracellular route,non saturable
• 5% ingested ca absorbed by this route
• Indirectly influenced by calcitriol
 Active Absorption Of Calcium
• Trancellular,receptor mediated ,25 % ingested ca absorption
• 1,25(OH)2D and caltriol mainly controls
• Trancellular calcium flux through apical TRPV6
• Calcium is rapidly and reversibly bound to calmodulinactin-
myosin I complex
• Calcium binds to calbindin
calbindin calcium complex dissociates the free intracelluar
calcium is actively extruded from the cell by Na-Ca
exchanger
• The glomerulus filters 9000 to 10000mg of complexed and ionized calcium in a 24
hr period

• The amount of calcium appearing in the urine is approx 250 mg / day

 Ca Reabsorption in PCT
• 1. Claudin 2 (Linked with Na+ absorption)

2. TRPV 6

Passive.

✓ Not influenced by factors or hormones.

✓ Inlfuenced by Na+
•

-- low salt diet in calcium stones

-- NS in hypercalcemia
 Ca Reabsorption in Loop OF Henle
Passive transport

Paracellular Claudin 16,19 -

• Driven by positive transepithelial potential generated by NKCC2

LOF mutations - FHHNC

Ca, Mg

Regulation mainly by ECF, little by hormones.

 Ca Reabsorption in Distal Tubule
• Active transport

Transcellular: TRPV5, TRPV6

Hormonally regulated by PTH, calcitonin and 1a,25(OH)2D3

 FACTORS CONTROLLING ABSORPTION

 Factors are classified into

1. Those acting on the mucosal cells

2. Those affecting the availability of

calcium and phosphates in the gut.
• LOOP DIURETICS

• Inhibits Na+-K+-2Cl- cotransporter type 2 → reduction in

lumen positivity that drives Ca2+ reabsorption →
HYPERCALCIURIA

THIAZIDE DIURETICS

⚫ reduction in extracellular fluid volume → secondarily

enhances Na+ and Ca2 reabsorption in PCT HYPOCALCIURIA
 HORMONAL CONTROL OF CALCIUM
& PHOSPHATE METABOLISM

HORMONES

PTH and 1a,25(OH)2D3 Increases the number

and activity of TRPV5 channels
 Vitamin D
• 1a,25(OH)2D3 increases the expression of  PTH
calbindin D9K and D28K and the PMCA pump
 Calcitonin
EXTRACELLULAR CALCIUM

Activation of Ca SR reduces renal tubular Ca2+

reabsorption & induces calciuresis

Regulation of the expression of claudin-14

which inhibits claudin 16,19
 VITAMIN D
 Cholecalciferol / D3
 Ergocalciferol / D2
 Can be called as hormone as it is produced in the skin
when exposed to sunlight.
 Vitamin D has very little intrinsic biological activity.

Vitamin D itself is not a active substance, instead it must be

first converted through a succession of reaction in the
liver and the kidneys to the final active product 1, 25 di
hydroxycholecalciferol.
DAILY REQUIRMENT

 Children & adults –400IU(10µg/day)

 Pregnancy and lactati on – 600IU(10µg/day)

 Over 70years- 800IU (20µg/day)

1microgram of vitamin D = 40 Internati onal

Units
 DIETARY SOURCE
 Cod liver oil
 Fish- Salmon
 Egg, liver

ACTIONS
 Mean action of vitamin D is to increase the plasma level of
calcium.
 Increases intestinal Ca&P absorption.
 Increases renal reabsorption of Calcium and phosphate.
VITAMIN D
7-DEHYDROCHOLESTEROL
UV radiation in sunlight Inhibited by melanin
VITAMIN D3
Bound to Vit D binding protein Transported to liver

25-Hydroxylase
25-D
1α Kidne
Hydroxylase y
1,25 D
Binds to intracellular
receptor
and forms a COMPLEX

CALCIUM
CALCIUM PHOSPHORUS
PHOSPHORUS BONE PTH Inhibitsits
Inhibits itsown
own
BONE PTH
absorptio absorption resorption secrn synthesisininkidney
absorptio absorption resorption secrn synthesis
nn kidney
 PARATHYROID HORMONE (PTH)

 Secreted by parathyroid gland

 Glands are four in number
 Present posterior to the thyroid
gland
 Combined weight of 130mg with
each gland weighing between 30-
50mg.
 PARATHYROID HORMONE (PTH)
 Histologically – two types of cells
• Chief cells (forming PTH)
• Oxyphilic cells (replaces the chief cells stores hormone)
 ACTIONS OF PTH
 The main function is to increase the level
of Ca in plasma within the critical range of
9 to11 mg.
 Parathormone inhibits renal phosphate re
absorption in the
proximal tubule and therefore increases
phosphate excretion
 Parathormone increases renal Calcium re
absorption in the distal tubule, which also
increases the serum calcium.

 Net effect of PTH  ↑ serum calcium

↓ serum phosphate
 STIMULATION FOR PTH SECRETION

 The stimulatory effect for PTH secretion is low level

of calcium in plasma.
 Maximum secretion occurs when plasma calcium level falls
below 7mg/dl.
 When plasma calcium level increases to 11mg/dl there is
decreased secretion of PTH
 CALCITONIN

 Minor regulator of calcium & phosphate metabolism

 Secreted by parafollicular cells or C-cells of thyroid gland.
 Also called as thyrocalcitonin.
 Single chain polypeptide
 Molecular weight 3400
 Plasma concentration – 10-20ug/ml
 ACTION OF CALCITONIN

 Net EFFECT of calcitonin  decreases Serum Ca

 Target site
-Bone (osteoclasts)
- decreased ability of osteoclasts to resorb bone

OSTEOCLASTS CELLS

◦ Lose their ruffled borders

◦ Undergo cytoskeletal
rearrangement
◦ Decreased mobility
◦ Detach from bone
• Calcitonin is a Physiological Antagonist to PTH with respect to
Calcium.
• With respect to Phosphate it has the same effect as PTH i.e.
↓
Plasma Phosphate level
EFFECTS OF OTHER HORMONES ON
CALCIUM METABOLISM

 GROWTH HORMONE

 INSULIN

 TESTOSTERONE & OTHER HORMONES

 LACTOGEN & PROLACTIN

 STEROIDS

 THYROID HORMONES
GROWTH HORMONE
 Increases the intestinal absorption of calcium and increases its excretion from

urine

 Stimulates production of insulin like growth factor in bone which stimulates

protein synthesis in bone

INSULIN
It is an anabolic hormone which favors bone formation

TESTOSTERONE
 Testosterone causes differential growth of cartilage resulting to
differential bone development
 Acts on cartilage & increase the bone growth.
 THYROID HORMONE
• In infants  stimulation of bone growth
• In adults  increased bone metabolism
 increased calcium mobilization

GLUCOCORTICOIDS

 Inhibit protein synthesis and so decrease bone formation

 Inhibit new osteoclast formation & decrease the activity of old osteoclasts.
 EXCRETION OF CALCIUM AND
PHOSPHOROUS
 Calcium is excreted in the urine, bile, and digestive secretions.
 The renal threshold for serum ca is 10 mg/dl.

Stools Urine
Unabsorbed
Sweat
calcium in 50-
the diet 15mg/day
200mg/day
60 – 70%
 Daily turnover rates of Ca in an adult
Intake 1000mg.
Intestinal absorption 350mg
Secretion in GI juice 250mg
Net absorption over secretion 100mg
Loss in the faeces 900mg
Excretion in the urine 80-100mg
 CAUSES OF HYPOCALCEMIA
IDIOPATHIC HYPOPARATHYROIDISM
It is an uncommon condition in which the parathyroid glands are absent or
atrophied. It may occur sporadically or as an inherited condition.

RENAL TUBULAR DISEASE

Including Fanconi's syndrome due to nephrotoxins such as heavy metals and
distal renal tubular acidosis, can cause severe hypocalcemia due to abnormal
renal loss of Ca and decreasing renal conversion to active vitamin D.

MAGNESIUM DEPLETION
Occurring with intestinal malabsorption or
dietary deficiency can cause hypocalcemia.

ACUTE PANCREATITIS
Causes hypocalcemia when Ca is chelated by
lipolytic products released from the inflamed
pancreas
HYPOPROTEINEMIA
Can reduce the protein-bound fraction of
plasma Ca. Hypocalcemia due to diminished
protein binding is asymptomatic

HYPERPHOSPHATEMIA
Also causes hypocalcemia by one or a variety of
poorly understood mechanisms. Patients with
renal failure and subsequent phosphate
retention are particularly prone to this form of
hypocalcemia
SEPTIC SHOCK
May be associated with hypocalcemia due to
suppression of PTH release
and conversion of 25(OH)D3 to 1,25(OH)2D3.

DRUGS
Associated with hypocalcemia include those
generally used to treat hypercalcemia
anticonvulsants (phenytoin, phenobarbital) and
rifampin, which alter vitamin D metabolism
 TETANY

It is characterized by sensory symptoms consisting of paresthesias of the lips,

tongue, fingers and feet; carpopedal spasm, which may be prolonged and
painful; generalized muscle aching; and spasm of facial musculature.

Tetany may be overt with spontaneous symptoms or latent and requiring

provocative tests to elicit. Latent tetany generally occurs at less severely
decreased plasma Ca concentrations: 7 to 8 mg/dL (1.75 to 2.20 mmol/L).
CHVOSTEK’S SIGN CARPOPEDAL SPASM

TROUSSEAU’S SIGN ACCOUCHER’S HAND

 Severe Asymptomati
symptomatic cases c cases
Calcium
Intravenou carbonat
s Calcium e
gluconate Vitamin D
•IV Calcium with continuous monitoring for arrhythmias till
S. Calcium >7mg/dl.
Inj. Calcium gluconate 10ml 10%/vol in 5% dextrose or NS
over 5 min.

•Oral Calcium and Vit D supplements

Elemental Calcium 1500mg/day
Vitamin D 50000-100000 U/ day or 2-3 times a week.
Classification of Causes of Hypercalcemia
B) Vit D related
A) PTH related
i) Vit D intoxication
i) Primarily hyperparathyroidism
ii) Increased 1,25 DHCC,
a) Solitary adenoma sarcoidosis.
b) Multiple endocrine neoplasia iii) Idiopathic
hypercalcemia of
ii) Lithium therapy infancy
iii) Familial hypocalcuric hypercalcemia

C) Malignancy related
i) Solid tumor with
metastasis
ii) Solid tumor with
humoral mediation of
hypercalcemia
D) Associated with High bone turn over
i) Hyperthyroidism

ii) Immobilization

iii) Thiazide

E) Association with renal failure

i) Severe secondary hyperparathyroidism

ii) Milk alkali syndrome

 REFERENCE

AK JAIN textbook of Physiology

Netters consice orthopeadics Anatomy Edition 9

Research gate and Microanatomy web atlas for

images
THANK YOU